Extracts from mammalian atrial tissue contain peptides, now referred to as atrial natriuretic factor(s), which posses natriuretic, diuretic, and vasorelaxant properties. Three bioactive atrial peptides, the atriopeptins, have been sequenced. Previous reports from other laboratories have been based on bolus injections of either atrial extracts or synthetic ANF peptides and have focused on decreases in blood pressure. Our experiments have utilized a constant infusion of atriopeptin III, the 24-amino acid form. We have found that the fall in mean arterial pressure is due predominately to a decrease in cardiac output. This is secondary to a fall in stroke volume with no change in heart rate and is accompanied by a rise in peripheral resistance and not a fall as others have hypothesized.